Airway Clearance Therapy on Hyperpolarized 129Xenon and MRI

This is an observational cohort study building on an existing protocol at our institution
recruiting CF patients who are 6-21 years old with one or two copies of the F508del CFTR
mutation. The existing protocol is funded by the NHLBI under R01-11863962 (PIs Woods, Clancy,
and hereafter referred to as "the NHLBI study" for simplicity), and seeks to enroll a total
of 38 subjects; it includes three to four (three scheduled, with a fourth optional) study
visits, with spirometry, LCI, UTE MRI, and 129Xe MRI being performed at each visit. This
present study will utilize existing study visits for the NHLBI study, with patients opting-in
to have all of the procedures performed twice, with an intervening ACT, during one their
study visits. The target enrollment is 20 subjects.

Airway clearance therapy (ACT) is used for treating cystic fibrosis (CF). It is known to
impact measures of lung function, and while an increasing number of lung function measures
are used in clinical trials, there has been no direct comparison of the effects of ACT across
the different modalities. This study is actively investigating the relationship between
different measures of lung function, comparing a spirometric measure (FEV1 percent-predicted)
with measures of whole-lung ventilation (lung clearance index, or LCI) and regional
assessments of both structure (with ultra-short echo time magnetic resonance imaging, or UTE
MRI) and function (with hyperpolarized xenon, or 129Xe, MRI). Performing these assessments on
CF patients will help to elucidate the relative sensitivity of each measure to
intra-individual changes within the lung and will help guide the selection of lung function
measures in future studies.

Inclusion Criteria:

- Male or female between the ages of 6 through 21 years

- CFTR genotypes as specified in NHLBI study:

Two copies of the F508del CFTR mutation, OR Two non-functional CFTR mutations with one of
them being F508del CFTR mutation

• Able to perform acceptable and repeatable spirometry

Exclusion Criteria:

- FEV1 percent predicted of <60%

- standard MRI exclusions (metal implants, claustrophobia)

- pregnancy